Minghua Liu, Farid Khasiyev, Antonio Spagnolo-Allende, Danurys L Sanchez, Howard Andrews, Qiong Yang, Alexa Beiser, Ye Qiao, Jose Rafael Romero, Tatjana Rundek, Adam M Brickman, Jennifer J Manly, Mitchell Sv Elkind, Sudha Seshadri, Christopher Chen, Oscar H Del Brutto, Saima Hilal, Bruce A Wasserman, Giuseppe Tosto, Myriam Fornage, Jose Gutierrez
{"title":"多群体全基因组关联研究发现与无症状颅内大动脉狭窄相关的多个新基因座。","authors":"Minghua Liu, Farid Khasiyev, Antonio Spagnolo-Allende, Danurys L Sanchez, Howard Andrews, Qiong Yang, Alexa Beiser, Ye Qiao, Jose Rafael Romero, Tatjana Rundek, Adam M Brickman, Jennifer J Manly, Mitchell Sv Elkind, Sudha Seshadri, Christopher Chen, Oscar H Del Brutto, Saima Hilal, Bruce A Wasserman, Giuseppe Tosto, Myriam Fornage, Jose Gutierrez","doi":"10.1177/17474930251374471","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Intracranial large artery stenosis (ILAS) is one of the most common causes of stroke worldwide and is associated with the risk for future vascular events. Asymptomatic ILAS is a frequent finding on neuroimaging and shares many risk factors with atherosclerotic vascular disease. Whether asymptomatic ILAS is driven by genetic variants is not well-understood.</p><p><strong>Methods: </strong>This study included 4960 participants from seven geographically diverse population-based cohorts (34% Whites, 16% African Americans, 22% Hispanics, 24% Asians, 5% native Ecuadorians). We defined asymptomatic ILAS as luminal stenosis >50% in any large brain artery using time-of-flight magnetic resonance angiography.</p><p><strong>Results: </strong>A genome-wide association study revealed one variant in <i>RP11-552D8.1</i> (rs75615271; odds ratio (OR), 1.22 (1.11-1.33); <i>p</i> = 4.85×10<sup>-8</sup>) associated with global ILAS at genome-wide significance (<i>p</i> < 5×10<sup>-8</sup>). Gene-based association analysis identified a gene-set enriched in chr1q32 region, including <i>NEK2</i>, <i>LPGAT1</i>, <i>INTS7</i>, <i>DTL</i>, and <i>TMEM206</i>, in global ILAS (<i>p</i> = 1.34 ×10<sup>-7</sup>) and anterior ILAS (<i>p</i> = 1.77 ×10<sup>-8</sup>).</p><p><strong>Discussion and conclusion: </strong>This study reveals one variant rs75615271 and a gene-set enriched in chr1q32 region associated with asymptomatic ILAS in a multi-population. Further functional studies may help elucidate the role that this variant plays in the pathophysiology of asymptomatic ILAS.</p>","PeriodicalId":14442,"journal":{"name":"International Journal of Stroke","volume":" ","pages":"17474930251374471"},"PeriodicalIF":8.7000,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multi-population genome-wide association study identifies multiple novel loci associated with asymptomatic intracranial large artery stenosis.\",\"authors\":\"Minghua Liu, Farid Khasiyev, Antonio Spagnolo-Allende, Danurys L Sanchez, Howard Andrews, Qiong Yang, Alexa Beiser, Ye Qiao, Jose Rafael Romero, Tatjana Rundek, Adam M Brickman, Jennifer J Manly, Mitchell Sv Elkind, Sudha Seshadri, Christopher Chen, Oscar H Del Brutto, Saima Hilal, Bruce A Wasserman, Giuseppe Tosto, Myriam Fornage, Jose Gutierrez\",\"doi\":\"10.1177/17474930251374471\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Intracranial large artery stenosis (ILAS) is one of the most common causes of stroke worldwide and is associated with the risk for future vascular events. Asymptomatic ILAS is a frequent finding on neuroimaging and shares many risk factors with atherosclerotic vascular disease. Whether asymptomatic ILAS is driven by genetic variants is not well-understood.</p><p><strong>Methods: </strong>This study included 4960 participants from seven geographically diverse population-based cohorts (34% Whites, 16% African Americans, 22% Hispanics, 24% Asians, 5% native Ecuadorians). We defined asymptomatic ILAS as luminal stenosis >50% in any large brain artery using time-of-flight magnetic resonance angiography.</p><p><strong>Results: </strong>A genome-wide association study revealed one variant in <i>RP11-552D8.1</i> (rs75615271; odds ratio (OR), 1.22 (1.11-1.33); <i>p</i> = 4.85×10<sup>-8</sup>) associated with global ILAS at genome-wide significance (<i>p</i> < 5×10<sup>-8</sup>). Gene-based association analysis identified a gene-set enriched in chr1q32 region, including <i>NEK2</i>, <i>LPGAT1</i>, <i>INTS7</i>, <i>DTL</i>, and <i>TMEM206</i>, in global ILAS (<i>p</i> = 1.34 ×10<sup>-7</sup>) and anterior ILAS (<i>p</i> = 1.77 ×10<sup>-8</sup>).</p><p><strong>Discussion and conclusion: </strong>This study reveals one variant rs75615271 and a gene-set enriched in chr1q32 region associated with asymptomatic ILAS in a multi-population. Further functional studies may help elucidate the role that this variant plays in the pathophysiology of asymptomatic ILAS.</p>\",\"PeriodicalId\":14442,\"journal\":{\"name\":\"International Journal of Stroke\",\"volume\":\" \",\"pages\":\"17474930251374471\"},\"PeriodicalIF\":8.7000,\"publicationDate\":\"2025-08-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Stroke\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17474930251374471\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Stroke","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17474930251374471","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Multi-population genome-wide association study identifies multiple novel loci associated with asymptomatic intracranial large artery stenosis.
Introduction: Intracranial large artery stenosis (ILAS) is one of the most common causes of stroke worldwide and is associated with the risk for future vascular events. Asymptomatic ILAS is a frequent finding on neuroimaging and shares many risk factors with atherosclerotic vascular disease. Whether asymptomatic ILAS is driven by genetic variants is not well-understood.
Methods: This study included 4960 participants from seven geographically diverse population-based cohorts (34% Whites, 16% African Americans, 22% Hispanics, 24% Asians, 5% native Ecuadorians). We defined asymptomatic ILAS as luminal stenosis >50% in any large brain artery using time-of-flight magnetic resonance angiography.
Results: A genome-wide association study revealed one variant in RP11-552D8.1 (rs75615271; odds ratio (OR), 1.22 (1.11-1.33); p = 4.85×10-8) associated with global ILAS at genome-wide significance (p < 5×10-8). Gene-based association analysis identified a gene-set enriched in chr1q32 region, including NEK2, LPGAT1, INTS7, DTL, and TMEM206, in global ILAS (p = 1.34 ×10-7) and anterior ILAS (p = 1.77 ×10-8).
Discussion and conclusion: This study reveals one variant rs75615271 and a gene-set enriched in chr1q32 region associated with asymptomatic ILAS in a multi-population. Further functional studies may help elucidate the role that this variant plays in the pathophysiology of asymptomatic ILAS.
期刊介绍：
The International Journal of Stroke is a welcome addition to the international stroke journal landscape in that it concentrates on the clinical aspects of stroke with basic science contributions in areas of clinical interest. Reviews of current topics are broadly based to encompass not only recent advances of global interest but also those which may be more important in certain regions and the journal regularly features items of news interest from all parts of the world. To facilitate the international nature of the journal, our Associate Editors from Europe, Asia, North America and South America coordinate segments of the journal.
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